EP1286667B1 - Zusammensetzungen zur verwendung bei der behandlung der osteoporose und/oder der entzündlichen gelenkerkrankungen - Google Patents

Zusammensetzungen zur verwendung bei der behandlung der osteoporose und/oder der entzündlichen gelenkerkrankungen Download PDF

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Publication number
EP1286667B1
EP1286667B1 EP01953150A EP01953150A EP1286667B1 EP 1286667 B1 EP1286667 B1 EP 1286667B1 EP 01953150 A EP01953150 A EP 01953150A EP 01953150 A EP01953150 A EP 01953150A EP 1286667 B1 EP1286667 B1 EP 1286667B1
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Prior art keywords
component
magnesium
calcium
acid
composition according
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French (fr)
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EP1286667A2 (de
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Herwig Buchholz
Jerzy Meduski
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Merck Patent GmbH
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Merck Patent GmbH
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/16—Inorganic salts, minerals or trace elements
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates, e.g., to compositions and pharmaceutical compositions for the treatment and/or prevention of inflammatory joint diseases, treating and/or preventing inflammatory joint diseases and the use of the aforementioned composition for the treatment and/or prevention of inflammatory joint diseases.
  • Osteoporosis (gr: osteon bone; poros hole) is described in general terms as a reduction in bone density with retention of a normal chemical composition. More specifically, osteoporosis is a generalized, progressive diminution of bone density, i.e. bone mass per unit volume, causing skeletal weakness, although the ratio of mineral to organic elements is unchanged. 30 to 40% of the skeletal mass must be lost in order to reliably diagnose osteoporosis by radiology. Contemporary medicine distinguishes between primary and secondary osteoporosis (The Merck Manual of Diagnosis and Therapy, 17th ed., 1999).
  • Primary osteoporosis includes idiopathic osteoporosis, rare but occurring in children and young adults; postmenopausal osteoporosis, occurring between the ages of 50 and 75; and involutional or senile osteoporosis associated with the normal process of aging. It is characterized by a predominant osteoclast activity and a disruption of the feedback mechanism between the serum calcium level and the parathyroid hormone (PTH) secretion. It occurs mainly uniformly throughout the whole skeleton. Secondary osteoporosis, accounting for less than 5% of all osteoporosis cases, includes endocrine dysfunctions. It starts mostly at the main skeleton and progresses centrifugally.
  • Osteoporosis is characterized by pain in the respective bones, diffuse back pain, vertebral body collapse, pathological fractures, in particular, fracture of the neck of the femur.
  • the goal of the management of all types of osteoporosis is therefore to decrease pain, to prevent fractures and to maintain the body functions.
  • osteoporosis is a calcium dysfunction and the use of calcium supplements has been widely suggested. However, so far, no reossification of the osteoporotic bone after calcium therapy could be demonstrated.
  • US-A-5,478,579 describes a method for inducing and enhancing the absorption of calcium into mammalian bone tissue in order to treat metabolic calcium deficiencies in bone tissue, in particular osteoporosis. It was found that ossification of mammalian bone tissue could be enhanced by orally administering to a patient an effective dose of calcium in combination with a flavonol aglycone glycoside. It is believed that the flavonol aglycone glycoside affords an advantageous function through a chelation delivery system. Flavonols possess a benzene ring structure having available bonds to function as a chelate.
  • flavonols due to their particular molecular structure, are capable of holding and delivering certain minerals, including calcium, to mammalian bone tissue. Also bone tissue would naturally absorb flavonol glycosides from the blood stream. It is further disclosed that the combination of the flavonol aglycone glycoside and calcium leads to an increased bone mineral density which would not have been obtainable through the use of simple calcium supplements.
  • quercetin which is a related bioflavonoid and differs from the aforementioned flavonol compounds in that it does not contain the glycoside residue, has been shown to inhibit tumor necrosis factor- ⁇ induced expression of interleukin 8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in cultured human synovial cells. It was therefore suggested that quercetin can be used in the treatment of rheumatoid arthritis which is an autoimmune disorder that involves inflammation mainly in synovial tissues of joints (Sato et al., The Journal of Rheumatology, 1997; 24:9, p. 1680).
  • IL-8 interleukin 8
  • MCP-1 monocyte chemoattractant protein-1
  • interleukin 1 is the most potent bone resorption agent. Although the role of interleukin 1, 6, 11 and the tumor necrosis factors is not quite clear, they appear to have a depressing effect on bone formation.
  • Homocysteinemia (the accumulation of homocysteine in plasma and tissue) is the result of deficiencies of certain enzymes and/or substrates involved in the transmethylation pathways. It is caused by the accumulation of homocysteine and its two disulfides in plasma and tissue (Mudd et al., The Metabolic Basis of Inherited Disease, New York, McGraw-Hill, 1978, p. 458). Homocysteinemia is associated with juvenile arteriosclerosis, recurrent arterial and venous thromboembolic manifestations and osteoporosis.
  • composition comprising the following components in combination:
  • the present invention provides also a pharmaceutical composition
  • a pharmaceutical composition comprising the following components in combination:
  • the present invention is directed to treating and/or preventing an inflammatory joint disease, comprising administering to a mammal in need thereof a therapeutically effective amount of a composition comprising the following components in combination:
  • composition comprising the following components in combination:
  • the composition comprises a component A comprising one or more of flavonol glycosides.
  • the flavonol glycosides contain a flavone skeleton of the following general structure of formula (1):
  • This skeleton forms the sugar-free part of the flavonoids and is also generally referred to as an aglycone.
  • Any aglycone can be used.
  • the aglycone is represented by formula (2) shown below: wherein R 1 and R 2 are independently hydrogen, hydroxy or a methoxy group.
  • R 1 and R 2 are independently hydrogen, hydroxy or a methoxy group.
  • These aglycones are preferred since they occur in nature and are, thus, readily available. Particularly preferred is the aglycone quercetin.
  • the flavonol glycoside contains a sugar residue which is bound via a glycosidic bond to the aglycone leading to structures of the formulae (3), (4) or (5) shown below.
  • R 1 and R 2 have the same meaning as described above and Gly is a mono- or oligoglycoside residue.
  • Gly represents a mono-, di- or triglycoside.
  • the glycoside is preferably selected from hexosyl residues, specifically rhamnesyl, glucosyl, galactosyl and mannosyl residues.
  • flavonol glycoside used in the present invention include glycosides of quercetin such as quercetin-3-O-galactoside (hyperoside), quercetin-3-O-glucoside (isoquercetin), quercetin-3-O-rhamnoside (quercitrin), quercetin-3-O-rutinoside (rutin), quercetin-7-O-glucoside (quercimeritrin), quercetin-4'-O-glucoside (spiraeosid) and quercetin-3-O-galactoside (hyperin).
  • quercetin-3-O-galactoside hyperoside
  • quercetin-3-O-glucoside isoquercetin
  • quercetin-3-O-rhamnoside quercitrin
  • quercetin-3-O-rutinoside quercetin-3-O-rutinoside
  • quercetin-7-O-glucoside querci
  • flavonol glycoside of the aglycone kaempferol kaempferol-3-O-glucoside (astragalin) may be mentioned.
  • Myricetin-3-O-digalactoside is an example of a flavonol glycoside of the aglycone myricetin.
  • An example of a flavonol glycoside of the aglycone isorhamnetin is isorhamnetin-3-O-rutinoside (narcissin).
  • the flavonol glycosides isoquercetin, quercetrin, isoquercetrin, quercimeritrin, spiraeosid, rutin and hyperin are particularly preferred.
  • the flavonol glycosides may be obtained from any source, e.g., plants, in particular herbs. Herbs known to contain for example quercetin glycosides are described in US-A-5,478,579.
  • composition according to the present invention comprises component A in an effective amount in order to exert the desired effect in the treatment and/or prevention of inflammatory joint diseases.
  • composition according to the present invention comprises component A in an effective amount in order to exert the desired effect in the treatment and/or prevention of osteoporosis and/or inflammatory joint diseases.
  • component A in an effective amount in order to exert the desired effect in the treatment and/or prevention of osteoporosis and/or inflammatory joint diseases.
  • an amount of about 0.1-25.0 weight % of the total, preferably about 0.2-12.5 weight %, and most preferably about 0.5-10.0 weight % is used.
  • the dosage of component A is preferably selected to comprise 25 to 1000 mg, preferably 40 to 500 mg per daily dose.
  • composition in accordance with the present invention comprises further a component B comprising one or more tetrahydrofolic acid compounds.
  • the tetrahydrofolic acid compound is a derivative of folic acid defined here under. Folic acid is metabolized in the body via dihydrofolic acid under the action of the enzyme dihydrofolate reductase into tetrahydrofolic acid.
  • the tetrahydrofolic acid compound is selected from tetrahydrofolic acid, 5-methyltetrahydrofolic acid, 5-formyltetrahydrofolic acid, 10-formyltetrahydrofolic acid, 5,10-methylenetetrahydrofolic acid, 5,10-methenyltetrahydrofolic acid or physiologically acceptable salts thereof.
  • the tetrahydrofolic acid compound may be used alone or as a mixture. It particularly preferred to use 5-formyltetrahydrofolic acid or physiologically acceptable salts thereof. Examples of physiologically acceptable salts are alkaline metal or alkaline earth metal salts, such as sodium or calcium salts.
  • Component B is present in the composition in accordance with the invention in an amount effective for the treatment and/or prevention of inflammatory joint diseases.
  • component B is present in an amount of about 0.002-0.15 weight % of the total, preferably about 0.004-0.07 weight % and most preferably about 0.01-0.02 weight %.
  • composition in accordance with the present invention comprises component B preferably in an amount of 400 to 5000 ⁇ g, more preferably 500 to 4000 ⁇ g per daily dose.
  • the composition in accordance with the present invention contains further a component C comprising one or more calcium supplements.
  • the calcium supplement is selected from elemental calcium and calcium compounds.
  • the calcium compound is selected from calcium oxide and calcium salts of organic or inorganic acids.
  • the calcium salts are calcium salts of inorganic acids, i.e. calcium carbonate, and calcium salts of organic acids i.e. calcium citrate, calcium lactate, calcium gluconate and, in particular, calcium salts of amino acids, viz. calcium glycinate and calcium lysinate.
  • Component C is present in the composition in accordance with the invention in an amount effective for the treatment and/or prevention of osteoporosis and/or inflammatory joint diseases.
  • component C is used in an amount of about 2.0-50.0 weight % of the total, preferably about 5.0-25.0 weight % and most preferably about 10.0-20.0 weight %.
  • composition in accordance with the present invention comprises component C preferably in an amount of 400 to 2000 mg, more preferably 500 to 800 mg per daily dose.
  • the composition of the present invention also comprises a component D comprising one or more magnesium supplements.
  • the magnesium supplement is selected from elemental magnesium and magnesium compounds.
  • magnesium compounds magnesium oxide and magnesium salts of organic or inorganic acids are employed.
  • Magnesium salts are magnesium salts of inorganic acids, i.e. magnesium glycerophosphate and magnesium chloride, and magnesium salts of organic acids i.e. magnesium citrate, magnesium lactate and magnesium gluconate and, in particular, magnesium salts of amino acids, i.e. magnesium glycinate and magnesium taurinate.
  • Component D is present in the composition of the invention in an effective amount for the treatment and/or prevention of osteoporosis and/or inflammatory joint diseases.
  • Component D is therefore typically used in an amount of about 0.5-30.0 weight % of the total, preferably about 1.2-25.0 weight % and most preferably about 2.5-17.5 weight % in the composition of the present invention.
  • composition of the present invention contains component D preferably in an amount of 100 to 1200 mg, more preferably 300 to 1000 mg per daily dose.
  • a pharmaceutical composition of the present application comprises the aforementioned components and additionally a pharmaceutically suitable carrier, diluent, vehicle and/or exipient.
  • the pharmaceutical composition is present in a suitable pharmaceutical form including solid, semi-solid, liquid or lyophilized formulations such as tablets, powders, capsules, suppositories, suspensions and aerosols.
  • the pharmaceutical form is a tablet or a capsule for oral administration.
  • suitable vehicles, carriers, diluents and/or excipients may be selected depending on the intended use.
  • compositions of the present invention are known to those skilled in the art.
  • pharmaceutical preparations may be prepared following conventional techniques of the pharmaceutical chemist involving steps such as mixing, granulating and compressing the necessary tablet forms, or mixing, filling and dissolving the ingredients as appropriate, to give the desired products for oral, parenteral, topical, transdermal, intravaginal, intranasal, intrabronchial, intraocular, intraaural and/or rectal administration.
  • steps such as mixing, granulating and compressing the necessary tablet forms, or mixing, filling and dissolving the ingredients as appropriate, to give the desired products for oral, parenteral, topical, transdermal, intravaginal, intranasal, intrabronchial, intraocular, intraaural and/or rectal administration.
  • Illustrative examples of such methods includes those described in Remington's Pharmaceutical Sciences, 18th edition (1990).
  • Solid or liquid pharmaceutically acceptable carriers, diluents, vehicles or excipients may be employed in the pharmaceutical compositions of the present invention.
  • Illustrative solid carriers include starch, lactose, calcium sulfate dihydrate, terra alba, sucrose, talc, gelatine, agar, pectin, acacia, magnesium stearate and stearic acid.
  • Illustrative liquid carriers include syrup, peanut oil, olive oil, saline solution and water.
  • the carrier or diluent may include a suitable prolonged release material such as glycerol monostearate or glycerol distearate, alone or with other auxiliaries.
  • the preparation may be in the form of a syrup, elixier, emulsion, soft gelatin capsule, sterile injectable liquid (e.g. solution) or a non-aqueous or aqueous liquid suspension.
  • compositions or pharmaceutical composition of the present invention is employed in the treatment and/or prevention of inflammatory joint diseases.
  • Administration of the composition of the pharmaceutical composition of the present invention may be performed according to any of the accepted modes of adminstration available to those skilled in the art.
  • suitable modes of administration include oral, nasal, parenteral, topical, transdermal, intravaginal, intranasal, intrabronchial, intraocular, intraaural and rectal.
  • the mode of administration is oral.
  • the specific dose for each patient depends on a wide variety of factors, for example on the activity of the specific compounds employed, the age, body weight, general state of health, sex, diet, the time and route of adminstration, the rate of excretion, the medicinal substance combination and severity of the particular disorder for which the therapy is applied.
  • the conditions or diseases which can be treated and/or prevented by the composition or pharmaceutical composition of the invention are inflammatory joint disease (e.g., rheumatoid arthritis, juvenile arthritis, infectious arthritis, ankylosing spondilitis, osteoarthritis, anrthralgias and other chronic inflammatory diseases associated with joint manifestations).
  • inflammatory joint disease e.g., rheumatoid arthritis, juvenile arthritis, infectious arthritis, ankylosing spondilitis, osteoarthritis, anrthralgias and other chronic inflammatory diseases associated with joint manifestations.
  • Advantages of the invention include, e.g., improved joint function (improved joint movement, decrease of morning stiffness, etc.) and reduced signs of inflammation (e.g., pain or swelling).
  • An oral formulation according to the invention is obtained by mixing:
  • An oral formulation according to the present invention is obtained by mixing:

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Claims (30)

  1. Zusammensetzung enthaltend:
    eine Komponente A, die ein oder mehrere Flavonolglycoside enthält,
    eine Komponente B, die ein oder mehrere aus Tetrahydrofolsäure, 5-Methyltetrahydrofolsäure, 5-Formyltetrahydrofolsäure, 10-Formyltetrahydrofolsäure oder 5,10-Methylentetrahydrofolsäure oder 5,10-Methenyltetrahydrofolsäure oder ein physiologisch unbedenkliches Salz davon enthält,
    eine Komponente C, die ein oder mehrere aus elementarem Calcium oder einer Calciumverbindung, die aus der Gruppe Calciumoxid, Calciumcarbonat, Calciumcitrat, Calciumlactat, Calciumgluconat, Calciumglycinat und Calciumlysinat ausgewählt ist, enthält,
    eine Komponente D, die ein oder mehrere aus elementarem Magnesium oder einer Magnesiumverbindung, die aus der Gruppe Magnesiumoxid, Magnesiumglycerophosphat, Magnesiumchlorid, Magnesiumcitrat, Magnesiumlactat, Magnesiumgluconat, Magnesiumglycinat und Magnesiumtaurinat ausgewählt ist, enthält.
  2. Zusammensetzung nach Anspruch 1, wobei die Komponente A ein oder mehrere aus einem Flavonolmono-, -di- oder -triglycosid enthaltend das Aglykon Quercetin, enthält.
  3. Zusammensetzung nach Anspruch 1, wobei die Komponente A Isoquercetin, Quercitrin, Isoquercitrin, Quercimeritrin, Spiraeosid, Rutin oder Hyperin ist.
  4. Zusammensetzung nach Anspruch 1, wobei die Komponente A 0,1-25,0 Gew.-% der Gesamtzusammensetzung ausmacht.
  5. Zusammensetzung nach Anspruch 1, wobei die Komponente B 5-Formyltetrahydrofolsäure oder ein physiologisch unbedenkliches Salz davon enthält.
  6. Zusammensetzung nach Anspruch 1, wobei die Komponente B 0,002-0,15 Gew.-% der Gesamtzusammensetzung ausmacht.
  7. Zusammensetzung nach Anspruch 1, wobei die Komponente C 2,0-50,0 Gew.-% der Gesamtzusammensetzung ausmacht.
  8. Zusammensetzung nach Anspruch 1, wobei die Komponente D 0,5-30,0 Gew.-% der Gesamtzusammensetzung ausmacht.
  9. Zusammensetzung nach Anspruch 1 zur Behandlung und/oder Vorbeugung einer entzündlichen Gelenkerkrankung.
  10. Zusammensetzung nach Anspruch 9, wobei die entzündliche Gelenkerkrankung aus der Gruppe rheumatoider Arthritis, juveniler rheumatoider Arthritis, psoriatischer Arthritis, Reiter-Syndrom, Morbus Crohn, Colitis ulcerosa, Sarkoidose, infektiöser Arthritis, Spondylitis ankylosans, Osteoarthritis und Anthralgien ausgewählt ist.
  11. Pharmazeutische Zusammensetzung enthaltend:
    eine Komponente A, die ein oder mehrere Flavonolglycoside enthält,
    eine Komponente B, die ein oder mehrere aus Tetrahydrofolsäure, 5-Methyltetrahydrofolsäure, 5-Formyltetrahydrofolsäure, 10-Formyltetrahydrofolsäure oder 5,10-Methylentetrahydrofolsäure oder 5,10-Methenyltetrahydrofolsäure oder ein physiologisch unbedenkliches Salz davon enthält,
    eine Komponente C, die ein oder mehrere aus elementarem Calcium oder einer Calciumverbindung, die aus der Gruppe Calciumoxid, Calciumcarbonat, Calciumcitrat, Calciumlactat, Calciumgluconat, Calciumglycinat und Calciumlysinat ausgewählt ist, enthält,
    eine Komponente D, die ein oder mehrere aus elementarem Magnesium oder einer Magnesiumverbindung, die aus der Gruppe Magnesiumoxid, Magnesiumglycerophosphat, Magnesiumchlorid, Magnesiumcitrat, Magnesiumlactat, Magnesiumgluconat, Magnesiumglycinat und Magnesiumtaurinat ausgewählt ist, enthält, und
    pharmazeutisch geeignete Träger, Verdünnungsmittel, Vehikel und/oder Hilfsstoffe.
  12. Pharmazeutische Zusammensetzung nach Anspruch 11, wobei die Komponente A ein oder mehrere aus einem Flavonolmono-, -di- oder -triglycosid enthaltend das Aglykon Quercetin, enthält.
  13. Pharmazeutische Zusammensetzung nach Anspruch 11, wobei die Komponente A Isoquercetin, Quercitrin, Isoquercitrin, Quercimeritrin, Spiraeosid, Rutin oder Hyperin ist.
  14. Pharmazeutische Zusammensetzung nach Anspruch 11, wobei die Komponente A 0,1-25,0 Gew.-% der Gesamtzusammensetzung ausmacht.
  15. Pharmazeutische Zusammensetzung nach Anspruch 11, wobei die Komponente B 5-Formyltetrahydrofolsäure oder ein physiologisch unbedenkliches Salz davon enthält.
  16. Pharmazeutische Zusammensetzung nach Anspruch 11, wobei die Komponente B 0,002-0,15 Gew.-% der Gesamtzusammensetzung ausmacht.
  17. Pharmazeutische Zusammensetzung nach Anspruch 11, wobei die Komponente C 2,0-50,0 Gew.-% der Gesamtzusammensetzung ausmacht.
  18. Pharmazeutische Zusammensetzung nach Anspruch 11, wobei die Komponente D 0,5-30,0 Gew.-% der Gesamtzusammensetzung ausmacht.
  19. Pharmazeutische Zusammensetzung nach Anspruch 11 zur Behandlung und/oder Vorbeugung einer entzündlichen Gelenkerkrankung.
  20. Pharmazeutische Zusammensetzung nach Anspruch 19, wobei die entzündliche Gelenkerkrankung aus der Gruppe rheumatoider Arthritis, juveniler rheumatoider Arthritis, psoriatischer Arthritis, Reiter-Syndrom, Morbus Crohn, Colitis ulcerosa, Sarkoidose, infektiöser Arthritis, Spondylitis ankylosans, Osteoarthritis und Anthralgien ausgewählt ist.
  21. Verwendung einer Zusammensetzung zur Herstellung eines Medikaments zur Behandlung und/oder Vorbeugung einer entzündlichen Gelenkerkrankung bei einem Säuger, wobei die Zusammensetzung enthält:
    eine Komponente A, die ein oder mehrere Flavonolglycoside enthält,
    eine Komponente B, die ein oder mehrere aus Tetrahydrofolsäure, 5-Methyltetrahydrofolsäure, 5-Formyltetrahydrofolsäure, 10-Formyltetrahydrofolsäure oder 5,10-Methylentetrahydrofolsäure oder 5,10-Methenyltetrahydrofolsäure oder ein physiologisch unbedenkliches Salz davon enthält,
    eine Komponente C, die ein oder mehrere aus elementarem Calcium oder einer Calciumverbindung, die aus der Gruppe Calciumoxid, Calciumcarbonat, Calciumcitrat, Calciumlactat, Calciumgluconat, Calciumglycinat und Calciumlysinat ausgewählt ist, enthält
    eine Komponente D, die ein oder mehrere aus elementarem Magnesium oder einer Magnesiumverbindung, die aus der Gruppe Magnesiumoxid, Magnesiumglycerophosphat, Magnesiumchlorid, Magnesiumcitrat, Magnesiumlactat, Magnesiumgluconat, Magnesiumglycinat und Magnesiumtaurinat ausgewählt ist, enthält.
  22. Verwendung nach Anspruch 21, wobei die entzündliche Gelenkerkrankung aus der Gruppe rheumatoider Arthritis, juveniler rheumatoider Arthritis, psoriatischer Arthritis, Reiter-Syndrom, Morbus Crohn, Colitis ulcerosa, Sarkoidose, infektiöser Arthritis, Spondylitis ankylosans, Osteoarthritis und Anthralgien ausgewählt ist.
  23. Verwendung nach Anspruch 21, wobei die Komponente A ein oder mehrere aus einem Flavonolmono-, -di- oder -triglycosid enthaltend das Aglykon Quercetin, enthält.
  24. Verwendung nach Anspruch 21, wobei die Komponente A ein oder mehrere aus Isoquercetin, Quercitrin, Isoquercitrin, Quercimeritrin, Spiraeosid, Rutin oder Hyperin enthält.
  25. Verwendung nach Anspruch 21, wobei die Komponente A 0,1-25,0 Gew.-% der Gesamtzusammensetzung ausmacht.
  26. Verwendung nach Anspruch 21, wobei die Komponente B 5-Formyltetrahydrofolsäure oder ein physiologisch unbedenkliches Salz davon enthält.
  27. Verwendung nach Anspruch 21, wobei die Komponente B 0,002-0,15 Gew.-% der Gesamtzusammensetzung ausmacht.
  28. Verwendung nach Anspruch 21, wobei die Komponente C 2,0-50,0 Gew.-% der Gesamtzusammensetzung ausmacht.
  29. Verwendung nach Anspruch 21, wobei die Komponente D 0,5-30,0 Gew.-% der Gesamtzusammensetzung ausmacht.
  30. Verwendung nach Anspruch 21, wobei der Säuger ein Mensch ist.
EP01953150A 2000-06-02 2001-05-19 Zusammensetzungen zur verwendung bei der behandlung der osteoporose und/oder der entzündlichen gelenkerkrankungen Expired - Lifetime EP1286667B1 (de)

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CA2410885C (en) 2010-07-13
EP1286667A2 (de) 2003-03-05
AU7566601A (en) 2001-12-11
CA2410885A1 (en) 2001-12-06
JP2003534373A (ja) 2003-11-18
ES2266220T3 (es) 2007-03-01
WO2001091734A8 (en) 2003-12-18
KR100814652B1 (ko) 2008-03-18
WO2001091734A2 (en) 2001-12-06
KR20040012430A (ko) 2004-02-11
US20030139354A1 (en) 2003-07-24
DE60120691D1 (de) 2006-07-27
WO2001091734A3 (en) 2002-12-05
ATE329587T1 (de) 2006-07-15
DE60120691T2 (de) 2007-06-06
BR0111210A (pt) 2003-12-16
US6812215B2 (en) 2004-11-02

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